Q
~ !
o
Scheme 18: Synthesis of methyl angolensate 1·28 from 7-deacetoxy-7-oxokhivorin 1·77 [68,69).
1.2.3.4.2
Class IVb: The Trijugln GroupQ
l~
§15 9 0 30o ,
6\. 7C02Me 1·78 trijugin B
o
Named after the trijugins from Heynea trijuga Roxb. [70] (syn. Trichilia connaroidesvar. connaroides (Wight et Am.) Sentv. [51]), members of this group have ring A intact, ring S opened, ring C
C~Me
Scheme 19: Synthesis of trijugin B ring by pinacol-pinacolone rearrangement.
1.2.3.4.3 Class IVe: The Mexieanolide Group
28 0
1·79 mexicanolide
o
MeOZ<;;
) ..
HO '.
~CY"
1-80 swietenine
o
OH
1-81 swietenolide
o
Members of this group have ringsA and C intact, a ring 0 lactone, and a B ring which has undergone rotation about the C-9,C-10 bond before recyclisation occurs by bond formation between C-2 and C- 30. The proposed biosynthetic pathway (scheme 20), involving spontaneous Michael addition of a ring A 1,3-diketone, has been experimentally substantiated in the laboratory, but does not explain how the naturally occurring isomeric swietenine 1-80 type compounds are formed, as synthetic attempts produce only the
a
8-double bond mexicanolide isomers, with no trace of the a8(3lJ)_ ora
14_double bond analogues [69,71,72] (scheme 21).
Many of the large number of these compounds that have been reported, despite being derivatives of earlier isolates (in particular, those with hydroxy substituents at C-2 and C-6), have been given trivial names of their own which have subsequently entered common usage. An example of this is
chapter 1 page 25 compound 1-81, which formally should be 3-deoxy-3p,6p-dihydroxymexicanolide, but which is found universally in the literature as swietenolide.
o
!
base0 -
ringArotation about
o •
~
Q
! 0---(0)i Q
!HO'"
o
1-79 mexica101ide
Scheme20:Biosynthesis of mexicanolide1-79 via G-9,C-10ringArotation andC-2,C-30Michael recyclisation [69,71,72].
o !
o
1·79 mexica101ide
o !
cr03
-
o
NaHC03
o •
Q
!
o
o
Scheme21:Laboratory synthesis of mexicanolide1-79 [69,71,72].
o
~02
1-82 utilin
Members of this group as it was originally defined [22] were analogues of either utilin 1-82, which was one of the very early limonoids isolated [24], or phragmalin 1·30 [73]. The structures of both were finally established only by X-ray crystallography [73,74].
The class IVd limonoids, as usual, have rings A and C intact and a ring 0 lactone. However, they possess also a 4,29,1-methylene bridge and an orthoacetate linkage, which occurs at 8,9,14 in utilin 1-82 and at 1,8,9 in phragmalin 1·30.
The biosynthesis of the phragmalin 1·30 1,8,9 Bring orthoacetate, as proposed by Taylor [75], was presumed to begin with a mexicanolide-like compound such as xyloccensin F 1-83, in which thed8(14L
double bond, having first been oxidised to give the 8a,14a-epoxide, had SUbsequently undergone acid-catalysed epoxide ring opening to give a d14-double bond and hydroxy group at C-8a, followed by reduction to the 14,15-dihydro derivative and nucleophilic attack on the ketone at C-1 to give the 1,8-ketal.
Abstraction of a hydrogen from the C-1 hydroxy group affords an oxygen radical, which initiates construction of the 4,29,1-bridge by a sequence offree radical H atom abstraction/oxidation reactions, and culminates in the formation of the 1,8,9-orthoacetate to give 3,30-diacetylphragmalin 1-84 (scheme 22).
chapter 1 page 27
OAe OAe reversionof1 ,8-kelalto
I
C-1ketone.Collahydroxy
+
formation of 4,29,1-bridge
Me02C
free radical at1ackonC-l
I.."
•
OAe OAe
Me02G
H-9 abstaction
I..
' ••
Me02C O ~~"-+...peroxide
I..
~,·OAe OAe
1.a3 xyloccensinF
Me02G
I..
'.!
C-9free radical hydroxylationMe02G
I..
"OAe
formation of 1,8,9- or1hoacelale
..
Me02G
I~'
. o
Scheme 22: Biosynthesis of 3.3O-diacetylphragmalin 1-84 from xyloccensin F 1-83 [75].
However. three compounds 1-85,1-86,1-87 that have recently been isolated from a Brazilian specimen ofKhaya senegalensis (Desr.) AJuss. [76.77] do not fit into Taylor's original classification [22] for the class IVc phragmalin group. nor do they fall into the mexicanolide class which lack the 4,29,i-bridge. Taylor's definition has thus been modified [23] to include compounds with the 4,29,1- bridge but not necessarily the 1.8.9- or 8.9, 14-orthoacetatet.
t This has alarming implications for the biosynthesis given in scheme 22. In his review [22]. Taylor quotes the example of tabularin from Chukrasia tabularis A.Juss [78] (not the flavone isolated from the same source by Purushothaman et al. [79]). which had been tentatively identified as having structure 1-88 on the basis of lH and13CNMR spectral analysis. He remarks:
•...tabularin. to which a ring A bridged structure unsubstituted at C8 or C9 has been ascribed. If this is correct, then the biosynthetic hypothesis is not correct in this case. and probably not in other cases."
He then weakens his own counterargument on the grounds that the missing C-1 ketone resonance upon which the structure of tabularin rests may be due to the weakness of the sample rather than the proposed structure. Taylor gave no structure for tabularin 1-88 in his discussion [22]. and the entry in his accompanying checklist is buried in a section labelled "Unknown or doubtful structures". which no doubt accounts for its absence both from the Dictionary of Natural Products (the entry given is to the flavone mentioned above) and from citation in the later publications [76,77].
o
1-85 R
=
R'=
H1-86 R = H, R' =Ac 1-87 R=Ac,R'=H
o o
1.2.3.4.5 Class IVe: The Entilin Group
19
o
18
f
1-33 entilinA
19
1-89 entilin D
Together with the group IVb trijugin group, this is the second subclass to be added [23] to the original Taylor classification [22]. Members of the class have been isolated from only one species to date, Entandrophragma utile (Dawe et Sprague), and currently number only four examples based on two structural templates, of which entilin A 1-33 and entilin D 1-89 are examples [80,81].
These compounds have only an intact ring C remaining of the original group IV criteria. Cleavage of the ring B C-9,G-10 bond, loss of the C-5 sidechain and ketal formation with the ring D lactone G-16 all combine to produce compounds which are amongst the most rearranged of all limonoids [23]
(scheme 23).
Meo;
HO'.
'.OH
chapter 1
o t
COO oxidation.
MeOj,..
o
OH
Baeyer-Villiger oxidation
!
page 29
Q
i
COS sidechain elimination
•
1.2.3.5
ketal formation